A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites

Baum, J; Richard, D; Healer, J; Rug, M; Krnajski, Z; Gilberger, TW; Green, JL; Holder, AA; Cowman, AF

Author(s): Baum, J; Richard, D; Healer, J; Rug, M; Krnajski, Z; Gilberger, TW; Green, JL; Holder, AA; Cowman, AF;
Details: Publication Year 2006-02-24,Volume 281,Issue #8,Page 5197-5208
Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY
Publication Type: Journal Article
Abstract: Apicomplexan parasites constitute one of the most significant groups of pathogens infecting humans and animals. The liver stage sporozoites of Plasmodium spp. and tachyzoites of Toxoplasma gondii, the causative agents of malaria and toxoplasmosis, respectively, use a unique mode of locomotion termed gliding motility to invade host cells and cross cell substrates. This amoeboid-like movement uses a parasite adhesin from the thrombospondin-related anonymous protein (TRAP) family and a set of proteins linking the extracellular adhesin, via an actin-myosin motor, to the inner membrane complex. The Plasmodium blood stage merozoite, however, does not exhibit gliding motility. Here we show that homologues of the key proteins that make up the motor complex, including the recently identified glideosome-associated proteins 45 and 50 (GAP40 and GAP50), are present in P. falciparum merozoites and appear to function in erythrocyte invasion. Furthermore, we identify a merozoite TRAP homologue, termed MTRAP, a micronemal protein that shares key features with TRAP, including a thrombospondin repeat domain, a putative rhomboid-protease cleavage site, and a cytoplasmic tail that, in vitro, binds the actin-binding protein aldolase. Analysis of other parasite genomes shows that the components of this motor complex are conserved across diverse Apicomplexan genera. Conservation of the motor complex suggests that a common molecular mechanism underlies all Apicomplexan motility, which, given its unique properties, highlights a number of novel targets for drug intervention to treat major diseases of humans and livestock.
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Keywords: PLASMODIUM-FALCIPARUM MEROZOITES; TOXOPLASMA-GONDII; ANONYMOUS PROTEIN; DIVERSIFYING SELECTION; CRYPTOSPORIDIUM-PARVUM; ERYTHROCYTE INVASION; GENOME SEQUENCE; THEILERIA-PARVA; HOST-CELLS; MYOSIN-A
Publisher's Version: https://doi.org/10.1074/jbc.M509807200
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Creation Date: 2006-02-24 12:00:00